Drug Delays Disability in MS

Action Points

Note that in this study of patients with relapsing-remitting multiple sclerosis, laquinimod treatment was associated with a modest reduction in the mean annualized relapse rate compared with placebo.

Note also that elevated levels of liver enzymes occurred twice as frequently in the laquinimod group, but were transient and were not associated with signs of liver failure.

The investigational oral multiple sclerosis drug laquinimod slows progression of disability and modestly reduces relapses in the relapsing-remitting form of the disease, researchers affirmed.

The annualized relapse rate was 0.30 per year with laquinimod compared with 0.39 among patients on placebo (P=0.001), Giancarlo Comi, M.D, of the University Vita-Salute San Raffaele in Milan, Italy, and colleagues found.

Risk of worsening disability fell 36% with the novel agent, at 11.1% versus placebo's 15.7% (P=0.01), they reported in the March 15 issue of the New England Journal of Medicine.

Those results from the ALLEGRO (Assessment of Oral Laquinimod in Preventing Progression in Multiple Sclerosis) study matched results initially reported at the American Academy of Neurology meeting last year.

The second pivotal phase III trial with the drug in relapsing-remitting multiple sclerosis, BRAVO, missed its primary endpoint for reducing relapses but significantly delayed progression of disability and brain atrophy, as reported at the ECTRIMS meeting later in 2011.

Those results along with a lack of immunosuppression have stirred hope that the novel drug could be used as an add-on agent, which has been considered too dangerous with current multiple sclerosis medications.

The ALLEGRO trial included 1,106 patients with relapsing-remitting multiple sclerosis randomized to double-blind treatment with a once daily oral dose of laquinimod (0.6 mg) or placebo for 24 months.

Similar to the primary endpoint of annualized relapse rate, the proportion of relapse-free patients was higher with laquinimod in the trial, at 63% compared with 52% with placebo (P<0.001).

The risk of relapse also fell significantly with laquinimod with a hazard ratio of 0.72 compared with placebo (P<0.001).

Along with the decrease in confirmed disability progression sustained for at least three months, the proportion of patients found to have progressed by their final assessment was lower with the drug at 10% versus 14% (P=0.04).

The effect on the brain was positive too. Laquinimod was associated with:

A reduction in cumulative number of gadolinium-enhancing lesions (1.33 versus 2.12, P<0.001)

With regard to adverse events, no patients died with laquinimod whereas three occurred with placebo.

The serious adverse event rate was 11.1% versus 9.5% with placebo.

More cases of cancer were seen with laquinimod, at eight compared with six (1.5% versus 1.1%), although not statistically significant and with no predominance of any one type of tumor. Appendicitis also occurred more often with the drug at five cases versus one with placebo.

The most common adverse events with laquinimod included:

Abdominal pain (5.8% versus 2.9%)

Back pain (16.4% versus 9.0%)

Cough (7.5% versus 4.5%)

Elevated levels of liver enzymes were also more common on laquinimod, with alanine aminotransferase three to five times the upper limit of normal in 3.6% versus 0.4% of patients with placebo. But these elevations were transient and without imaging or laboratory signs of liver failure.

Further long-term studies are needed to adequately determine the risk of infections and cancers with the drug, the researchers noted.

The study was supported by Teva Pharmaceuticals.

Comi reported receiving consulting fees or honoraria and travel support from Teva and consulting for Bayer Schering, Merck Serono, sanofi-aventis, Biogen Dompè, and Novartis as well.